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Stahl, E.A.* ; Wegmann, D.* ; Trynka, G.* ; Gutierrez-Achury, J.* ; Do, R.* ; Voight, B.F.* ; Kraft, P.* ; Chen, R.* ; Kallberg, H.J.* ; Kurreeman, F.A.* ; DIAGRAM Consortium (Grallert, H. ; Huth, C. ; Gieger, C. ; Klopp, N. ; Thorand, B. ; Wichmann, H.-E. ; Petersen, A.-K. ; Illig, T.) ; Myocardial Infarction Genetics Consortium (*) ; Kathiresan, S.* ; Wijmenga, C.* ; Gregersen, P.K.* ; Alfredsson, L.* ; Siminovitch, K.A.* ; Worthington, J.* ; de Bakker, P.I.* ; Raychaudhuri, S.* ; Plenge, R.M.*

Bayesian inference analyses of the polygenic architecture of rheumatoid arthritis.

Nat. Genet. 44, 483-489 (2012)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
The genetic architectures of common, complex diseases are largely uncharacterized. We modeled the genetic architecture underlying genome-wide association study (GWAS) data for rheumatoid arthritis and developed a new method using polygenic risk-score analyses to infer the total liability-scale variance explained by associated GWAS SNPs. Using this method, we estimated that, together, thousands of SNPs from rheumatoid arthritis GWAS explain an additional 20% of disease risk (excluding known associated loci). We further tested this method on datasets for three additional diseases and obtained comparable estimates for celiac disease (43% excluding the major histocompatibility complex), myocardial infarction and coronary artery disease (48%) and type 2 diabetes (49%). Our results are consistent with simulated genetic models in which hundreds of associated loci harbor common causal variants and a smaller number of loci harbor multiple rare causal variants. These analyses suggest that GWAS will continue to be highly productive for the discovery of additional susceptibility loci for common diseases.
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Publication type Article: Journal article
Document type Scientific Article
Keywords GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; CELIAC-DISEASE; GENETIC SUSCEPTIBILITY; MISSING HERITABILITY; HEART-DISEASE; HUMAN HEIGHT; COMMON SNPS; RISK LOCI; VARIANTS
Language english
Publication Year 2012
HGF-reported in Year 2012
ISSN (print) / ISBN 1061-4036
e-ISSN 1546-1718
Journal Nature Genetics
Quellenangaben Volume: 44, Issue: 5, Pages: 483-489 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)
Institute of Genetic Epidemiology (IGE)
Research Unit Molecular Epidemiology (AME)
POF-Topic(s) 30202 - Environmental Health
30503 - Chronic Diseases of the Lung and Allergies
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-504000-002
G-503900-001
G-504100-001
G-504200-003
G-504200-002
PubMed ID 22446960
DOI 10.1038/ng.2232
WOS ID 000303416300006
Erfassungsdatum 2012-06-19
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